Colchicine Tablets

General Notices

Definition

Colchicine Tablets contain Colchicine.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of colchicine, C22H25NO6

95.0 to 105.0% of the stated amount.

Identification

A. Extract a quantity of the powdered tablets containing 5 mg of Colchicine with 50 mL of methanol (50%), filter through a 0.2-µm nylon filter and dilute 10 mL of the filtrate to 100 mL with methanol (50%). The light absorption, Appendix II B, in the range 220 to 400 nm exhibits two maxima, at 246 nm and 352 nm.
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) corresponds to that of the principal peak in the chromatogram obtained with solution (2).

TESTS

Dissolution

Comply with the dissolution test for tablets and capsules, Appendix XII B1.

test conditions
(a) Use Apparatus 2, rotating the paddle at 75 revolutions per minute.
(b) Use 500 mL of a pH 6.8 buffer prepared by mixing 3.52 g of sodium dihydrogen orthophosphate monohydrate and 4.35 g of disodium hydrogen orthophosphate dihydrate with sufficient water to produce 1000 mL, at a temperature of 37°, as the medium.
procedure

Carry out the method for liquid chromatography, Appendix III D, using the following solutions protected from light.

(1) After 45 minutes withdraw a sample of the medium and filter. Use the filtered medium, diluted with the dissolution medium if necessary, to produce a solution expected to contain 0.0001% w/v of colchicine.
(2) 0.0001% w/v of colchicine BPCRS in the dissolution medium.
chromatographic conditions

The chromatographic conditions described under Related substances may be used. Inject 50 µL of each solution and use a detection wavelength of 243 nm.

determination of content

Calculate the total content of colchicine, C22H25NO6, in the medium from the chromatograms obtained and using the declared content of C22H25NO6 in colchicine BPCRS.

limits

The amount of colchicine released is not less than 75% (Q) of the stated amount.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions in methanol (50%) protected from light.

(1) Extract a quantity of the powdered tablets containing 5.0 mg of Colchicine in 40 mL with the aid of ultrasound, dilute to 50 mL and filter through a 0.2-µm membrane filter.
(2) Dilute 1 volume of solution (1) to 100 volumes.
(3) Dilute 1 volume of solution (2) to 10 volumes.
(4) Dissolve 5 mg of colchicine for system suitability EPCRS in 5 mL.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5µm) (Lichrosorb RP8 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
mobile phase
Mobile phase Awater.
Mobile phase Bmethanol.

When the chromatograms are recorded under the prescribed conditions the retention time relative to colchicine (retention time about 13 minutes) is: impurity A, about 0.9.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between impurity A and colchicine is at least 1.5.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to impurity A is not greater than 3.5 times the area of the principal peak in the chromatogram obtained with solution (2) (3.5%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%);

the sum of the areas of all of the secondary peaks is not greater than 5 times the area of the principal peak in the chromatogram obtained with solution (2) (5%).

Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (3) (0.1%).

Uniformity of content

Tablets containing less than 2 mg and/or less than 2% w/w of Colchicine comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in methanol (50%) protected from light.

(1) Transfer 1 tablet to a 5 mL volumetric flask. Add about 4 mL, disperse with the aid of ultrasound, dilute to volume and filter through a 0.2-µm membrane filter.
(2) 0.01% w/v of colchicine BPCRS.
(3) Dissolve 5 mg of colchicine for system suitability EPCRS in 5 mL.
chromatographic conditions

The chromatographic conditions described under Related substances may be used.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between impurity A and colchicine is at least 1.5.

determination of content

Calculate the content of C22H25NO6 in each tablet using the declared content of C22H25NO6 in colchicine BPCRS.

Assay

Use the average of the individual results determined in the test for Uniformity of content.

Impurities

The impurities limited by the requirements of this monograph include those listed under Colchicine.

Storage

Colchicine Tablets should be protected from light.